# US 2021/0080452 A1 · NMR Measurements of NMR Biomarker GlycA

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- Number: US 2021/0080452 A1
- Document ID: US20210080452A1
- Status: Published application
- Kind: A1
- Application number: 17/097,640
- Filed: 2020-11-13
- Published: 2021-03-18
- Earliest claimed: 2012-06-08
- Assignees: LipoScience, Inc.
- Applicants: LipoScience, Inc.
- Inventors: James D. Otvos; Irina Y. Shalaurova; Dennis W. Bennett; Justyna E. Wolak-Dinsmore
- Web page: https://patentgrep.com/patent/US20210080452A1

## CPC

- G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)}
- A61B 5/0044: {for the heart}
- A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
- A61B 5/7275: {Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor}
- G01N 24/08: by using nuclear magnetic resonance (G01N24/12 takes precedence)
- G01R 33/4625: {Processing of acquired signals, e.g. elimination of phase errors, baseline fitting, chemometric analysis}
- G01R 33/465: applied to biological material, e.g. in vitro testing
- G16H 50/30: for calculating health indices; for individual health risk assessment
- A61B 2576/023: for the heart
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- G01N 2333/4728: alpha-Glycoproteins
- G01N 2800/324: Coronary artery diseases, e.g. angina pectoris, myocardial infarction
- G01N 2800/50: Determining the risk of developing a disease
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA

## Abstract

Biomarkers and/or risk assessments identify patients having an increased risk of certain clinical disease states including, for example, CHD, type 2 diabetes, dementia, or all-cause death (ACD) using NMR signal to measure a level of “GlycA” in arbitrary units or in defined units (e.g., μmol/L) that can be determined using a defined single peak region of proton NMR spectra. The GlycA measurement can be used as an inflammation biomarker for clinical disease states. The NMR signal for GlycA can include a fitting region of signal between about 2.080 ppm and 1.845 ppm of the proton NMR spectra.

## Claims

### Claim 1

A method of measuring GlycA, comprising:
electronically obtaining a composite NMR spectrum of a fitting region of a biosample of a subject;
electronically deconvolving the composite NMR spectrum using a defined deconvolution model with high density lipoprotein (HDL) components, low density lipoprotein (LDL) components, VLDL (very low density lipoprotein)/chylomicron components, and a plurality of curve fit functions associated with at least a GlycA peak region; and
electronically generating a measure of GlycA using the curve fit functions.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The method of claim 1, wherein the curve fit functions are overlapping Lorentzian functions, and wherein the measure of GlycA is generated by summing a defined number of Lorentzian functions.

### Claim 4 (depends on 1)

The method of claim 1, wherein the deconvolution model further comprises a protein signal component for protein having a density greater than 1.21 g/L.

### Claim at position 5

5-8. (canceled)

### Claim 9 (depends on 1)

The method of claim 1, wherein the biosample comprises blood plasma or serum, wherein the electronically obtaining comprises obtaining NMR signal of the biosample while the biosample is at 47 degrees C.+/−0.2 degrees in an NMR flow probe of an NMR spectrometer, and wherein the fitting region extends from 1.845 ppm to 2.080 ppm, and wherein the GlycA peak region is centered at 2.00 ppm and wherein the method further comprises summing a defined number of a different set of curve fitting functions to generate a measure of GlycB.

### Claim at position 7

10-27. (canceled)

### Claim 28

A system, comprising:
an NMR spectrometer for acquiring at least one NMR spectrum of an in vitro biosample; and
at least one processor in communication with the NMR spectrometer, the at least one processor configured to obtain an NMR measurement of GlycA using the at least one NMR spectrum.

### Claim 29 (depends on 28)

The system of claim 28, wherein the at least one processor is configured to:
(i) obtain a composite NMR spectrum of a fitting region of an in vitro plasma biosample;
(ii) deconvolve the composite NMR spectrum using a defined deconvolution model with high density lipoprotein (HDL), low density lipoprotein (LDL), VLDL (very low density lipoprotein)/chylomicron components, a defined protein signal component, and curve fitting functions associated with at least a GlycA peak region; and
(iii) electronically generate the NMR measurement of GlycA based on the curve fitting functions.

### Claim 30 (depends on 29)

The system of claim 29, wherein the curve fitting functions comprise overlapping Lorentzian functions, and wherein the at least one processor sums a defined number of the functions to generate the NMR measurement.

### Claim 31 (depends on 29)

The system of claim 29, wherein the at least one processor is configured to apply a conversion factor to the summed NMR measurement to generate a GlycA measurement in μmol/L.

### Claim 32 (depends on 30)

The system of claim 30, wherein the biosample is a blood plasma or serum sample, and wherein the at least one processor is configured to obtain a concentration measurement of high density lipoprotein particles (HDL-P) and a concentration measurement of low density lipoprotein particles (LDL-P).

### Claim 33 (depends on 28)

The system of claim 28, wherein the at least one processor is configured to deconvolve another part of the NMR spectrum of the sample associated with a quartet of valine signals and generate an NMR measure of valine.

### Claim 34 (depends on 28)

The system of claim 28, wherein the at least one processor is configured to generate patient reports summarizing a respective GlycA measurement and at least one lipoprotein subclass measurement and/or a Valine measurement.

### Claim 35 (depends on 28)

The system of claim 28, wherein the at least one processor is configured to use the GlycA measurement as a denominator in a defined all-cause death risk ratio and generate a risk number associated with a risk of all-cause death.

### Claim at position 16

36-38. (canceled)

### Claim 39

An NMR analyzer comprising:
a NMR spectrometer;
and
at least one processor in communication with the spectrometer configured to obtain NMR signal of a defined single peak region of NMR spectra associated with GlycA of a fluid specimen and generate a report providing a GlycA level.

### Claim 40 (depends on 39)

The NMR analyzer of claim 39, wherein the at least one processor is configured to carry out the following or is in communication with at least one local or remote processor that is configured to carryout out the following: (i) deconvolve a composite NMR spectrum using a defined deconvolution model with high density lipoprotein (HDL), low density lipoprotein (LDL), VLDL (very low density lipoprotein)/chylomicron components, a defined protein signal component, and curve fitting functions associated with at least a GlycA peak region; and (ii) electronically generate the GlycA level.

### Claim 41 (depends on 39)

The NMR analyzer of claim 39, wherein the curve fitting functions comprise overlapping Lorentzian functions, and the at least one processor is configured to sum a defined number of the functions to generate the GlycA level.

### Claim 42

(canceled)

### Claim 43 (depends on 39)

The NMR analyzer of claim 39, wherein the at least one processor is configured to (a) deconvolve a composite NMR spectrum using a defined deconvolution model with high density lipoprotein (HDL) components, low density lipoprotein (LDL) components, VLDL (very low density lipoprotein)/chylomicron components, and curve fit functions associated with at least a GlycA peak region to provide the GlycA level and (b) deconvolve another part of the NMR spectrum of the sample associated with a quartet of valine signals and generate an NMR measure of valine.

### Claim 44 (depends on 39)

The NMR analyzer of claim 39, wherein the at least one processor is configured to (i) deconvolve an NMR spectrum using a defined deconvolution model with high density lipoprotein (HDL) components, low density lipoprotein (LDL) components, VLDL (very low density lipoprotein)/chylomicron components, and metabolite A components, and (ii) sum a plurality of values of a defined subset of curve fit functions associated with a GlycA fitting regions to provide the GlycA level.

### Claim 45 (depends on 39)

The NMR analyzer of claim 39, wherein the at least one processor is configured to apply a plurality of curve fit functions to a fitting region that includes the GlycA peak region and extends to a GlycB peak region with between about 40-60 curve fit functions, and wherein the GlycA level is calculated by summing values of a defined first subset of the curve fit functions and applying a defined conversion value.

### Claim 46

(canceled)

### Claim 47 (depends on 39)

The NMR analyzer of claim 39, wherein the at least one processor fa configured to calculate a ratio of measurements using at least one of the following: valine/GlycA, HDL-P/GlycA or (Valine*HDL-P)/GlycA.

### Claim at position 26

48-53. (canceled)